Insufficient Responses Research Articles

July 2023

July 2023

Employees’ perception towards e-learning: an exploratory study in the information technology sector in India

PurposeThe primary purpose of this research paper is to evaluate e-learning among employees of Information Technology (IT) companies based in Hyderabad, India.Design/methodology/approachA survey was undertaken among the employees from different IT companies based in Hyderabad, India, to gauge the perception towards e-learning. The participants were selected randomly. The evaluation is based on a few factors: convenience, usefulness, course content, quality, effectiveness and benefits for employees and organizations. The responses were recorded online through a structured questionnaire. In total, 237 responses have been collected for this present study, of which 227 questionnaires were used for analysis.FindingsThe surveyed employees perceived that e-learning helped them enhance their workplace competency in a flexible but effective manner. The e-learning also empowered the learners and ultimately contributed to the enhancement of organizational performance in some ways.Research limitations/implicationsLimitation of the study – by examining the pris study was confined to employees working with IT companies based in Hyderabad City, India. The data is collected online, and there may be some insufficient responses. Implications of the study – the study results show a deep insight into the critical aspects of e-learning as a tool for employee training for the benefit of employees and organizational development. The surveyed respondents from the IT sector at Hyderabad perceived that keys to successful e-learning programs should give due consideration towards availability of internet bandwidth, making the course more interactive, providing more choices to the learners and user-friendly and personalized learning experience. The study also shows that the e-learning programs primarily benefit the employees as well as the organization in a manner, namely, improved productivity, helping to achieve business objectives of the firm, growth and advancement to the employees and enhancing the job-related knowledge. The study also discovered that e-learning improves employees’ opportunities for professional growth and advancement inside and outside the organization by assisting them in learning new skills and enhancing job-related information.Practical implicationsThe internet penetration in recent years, as well as post-Covid-19, has given rise to online learning in the education and corporate sectors. The emergence of online or e-learning has been gaining ground in the corporate world by replacing the existing face-to-face or physical training model because of the cost factor and flexible learning to the learners. E-learning improves the learner’s ability to adapt to the company’s constantly changing business environment, which in turn helps the company increase departmental productivity and, ultimately, achieve its overall business goals.Social implicationsThe e-learning also empowered the learners and ultimately contributed to the enhancement of organizational performance in some ways. The e-learning also empowers the learner to perform better at his workplace and at the same time moving on the social ladder as the learning makes him/her confident at the job market.Originality/valueThis study provides a valuable understanding of employee perceptions on the adoption and effectiveness of e-learning, which ultimately improves the benefits of the training and development department in realizing and enhancing the quality in corporate companies.

Investigation of coated 316L steel surface: Surface morphology, composition, corrosion, and biocompatibility using hydroxyapatite mixed-EDM process

316L stainless steel belongs to insufficient biological responses and corrosion resistance. Although hydroxyapatite powder (HAp)-based coating improves biological responses and corrosion resistance of the 316L stainless steel, these coatings have resulted in inferior adhesion strength and cracked surface. This study aims to synthesize a highly biocompatible and corrosion resistant coating on the 316L stainless steel with a high adhesion strength and surface integrity using the electro discharge machining (EDM) method. The study also aims to explore the impacts of process parameters on the surface features. To reach the set objectives, several characterisation methods including atomic force microscopy (AFM), scanning electronic microscopy (SEM), X-ray powder diffraction (XRD), Potentiostat (electrochemical cell), MTT assay and X-ray photoelectron spectroscopy (XPS) were adopted. The HAp-mixed EDM method synthesized a biocompatible and corrosion resistant coating with an average thickness of 14.6 μm and 20.8 MPa adhesion strength comprising of Ca-P based oxides and carbides. The modified surface showed nano surface roughness of 18.5 nm. The oxides and carbides formed in the coating improved the cell viability of 316L stainless steel surface to 87 % and corrosion resistance to 0.00123 mm per year. This study is trying to gain the attention of 316L stainless steel-based bioimplant manufacturers to launch the hydroxyapatite mixed-EDM method for concurrent machining and coating.

PROTEOMIC PROFILING IDENTIFIES GRANZYME B INHIBITOR SERPIN B9 AS MEDIATOR OF RESISTANCE TO CAR T‐CELL AND BISPECIFIC ANTIBODY TREATMENT IN NODAL B‐CELL LYMPHOMA

Introduction: Treatment options for relapsed or refractory (r/r) B-cell non-Hodgkin lymphomas (B-NHL) have broadened towards T-cell engaging therapies, including CD19-targeting chimeric antigen receptor T-cells (CD19-CAR) and bispecific antibodies (CD19-BsAb). Although CD19-CAR and CD19-BsAb induce durable responses in some r/r B-NHL patients, response remains heterogenous and a significant proportion of patients experience insufficient responses or relapse. A thorough understanding of tumor-intrinsic mechanisms of resistance is crucial for the clinical improvement of T-cell immunotherapy. Methods: Aiming to identify lymphoma cell-inherent mechanisms that impair response to T-cell engaging therapy, we quantified the in-vitro response of 46 B-NHL cell lines to 3rd generation CD19-CAR and CD19-BsAb. Response was measured using a high-throughput flow cytometry-based assay. In parallel, cell lines were subjected to proteomic profiling and protein abundance was regressed on in-vitro response in order to identify proteomic determinants of response. We further combined CD19-CAR treatment with clinically relevant drugs and assessed how killing of lymphoma cells and expansion of T-cells was altered. Results: Response to CD19-CAR and CD19-BsAb was highly heterogeneous across cell lines and B-NHL entities, but not significantly linked to their proliferation rate or CD19 expression. Integration of the proteomic profiles revealed that abundance of Serpin B9, endogenous inhibitor of T-cell effector molecule granzyme B, was associated with poor response to CD19-CAR and CD19-BsAb. This finding was validated in overexpression and knock-out models. Overexpression of SERPINB9 indeed attenuated response to CD19-CAR and CD19-BsAb, while its knock-out rendered cell lines more sensitive. The observed changes in susceptibility to T-cell-mediated cytotoxicity upon modulation of SERPINB9 expression were independent of T-cell donor and expression of T-cell activation and proliferation markers. We sought to improve T-cell-mediated cytotoxicity specifically in samples with high SERPINB9 expression and found that immune checkpoint inhibitors and lenalidomide enhanced expansion of CAR T-cells and increased killing of lymphoma cells. In addition, vorinostat and antibody-drug-conjugate polatuzumab vedotin specifically killed lymphoma cells without affecting T-cell expansion. However, the observed improvement in T-cell-mediated cytotoxicity was independent of SERPINB9 expression. Keywords: aggressive B-cell non-Hodgkin lymphoma, immunotherapy, indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Perceived Seriousness Of Wrongdoing And Peer Reporting Intention: The Moderating Role Of Wrongdoer’s Status

Main Purpose - This study intends to evaluate the moderating effect of wrongdoer status (close friends or acquaintances) on the link between perceived wrongdoing seriousness and intention to report academic misconductMethod - This research used a 1x2 experimental design between subjects. One hundred eleven participants from three universities were involved in the experiments. Participants were selected using a method of purposive sampling. However, only 106 responses can be analyzed using SMART PLS 4 due to insufficient responses from some participants.Main Findings - The findings indicate that students are more likely to report academic misconduct when they consider it to be more severe. However, if the perpetrator is a close friend, the likelihood of a student reporting academic misconduct is significantly reduced.Theory and Practical Implications – This study has consequences for how colleges respond when students report their friends for academic dishonesty. Students fear that if they report the inappropriate activity of their close friends, they would be left by their friends. Educating students and faculty members on the need of recognizing and reporting academic dishonesty could contribute to the creation of an ethical university culture.Novelty – Prior research has often been descriptive and qualitative, meanwhile, this study applies path analysis to provide empirical evidence specifically in the Indonesian context about the impact of friendship on students' willingness to report academic misconduct.

Long term follow-up of humoral and cellular response to mRNA-based vaccines for SARS-CoV-2 in patients with active multiple myeloma.

Long-term kinetics of antibody (Ab) and cell-mediated immune (CMI) response to full anti-SARS-CoV-2 vaccine schedule and booster doses in Multiple Myeloma (MM) patients remain unclear. We prospectively evaluated Ab and CMI response to mRNA vaccines in 103 SARS-CoV-2-naïve MM patients (median age 66, 1 median prior line of therapy) and 63 health-workers. Anti-S-RBD IgG (Elecsys®assay) were measured before vaccination and after 1 (T1), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months from second dose (D2) and 1 month after the introduction of the booster dose (T1D3). CMI response (IGRA test) was evaluated at T3 and T12. Fully vaccinated MM patients displayed high seropositivity rate (88.2%), but low CMI response (36.2%). At T6 the median serological titer was halved (p=0.0391) in MM patients and 35% reduced (p=0.0026) in controls. D3 (94 patients) increased the seroconversion rate to 99% in MM patients and the median IgG titer in both groups (up to 2500 U/mL), maintained at T12. 47% of MM patients displayed a positive CMI at T12 and double-negativity for humoral and CMI (9.6% at T3) decreased to 1%. Anti-S-RBD IgG level ≥346 U/mL showed 20-times higher probability of positive CMI response (OR 20.6, p<0.0001). Hematological response ≥CR and ongoing lenalidomide maintenance enhanced response to vaccination, hindered by proteasome inhibitors/anti-CD38 monoclonal antibodies. In conclusion, MM elicited excellent humoral, but insufficient cellular responses to anti-SARS-CoV-2 mRNA vaccines. Third dose improved immunogenicity renewal, even when undetectable after D2. Hematological response and ongoing treatment at vaccination were the main predictive factors of vaccine immunogenicity, emphasizing the role of vaccine response assessment to identify patients requiring salvage approaches.

Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection.

With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer. This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes. CRP(P<0.001), D-dimer (P<0.001), ferritin (P=0.039), and hemoglobin (P=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (P<0.001). However, plasmapheresis did not affect the length of hospital stay (P=0.076), which could have significantly increased survival rates (P<0.001). Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.

Iterative hypothesis testing in HIV vaccine research: moving towards success.

Iterative hypothesis testing in HIV vaccine research: moving towards success.

カルバマゼピン中毒により下眼瞼向き眼振を認めた薬剤性めまい症例

We report the case of a 33-year-old man who presented with disequilibrium and downbeat nystagmus. Balance testing showed failure of visual suppression of caloric nystagmus with insufficient optokinetic nystagmus responses, suggesting central vestibular dysfunction. However, MRI showed no lesions in the brain, including in the cerebellum. The patient had been diagnosed previously as having epilepsy, and the convulsions had remained under control for more than 10 years with a maintenance dose of carbamazepine (900mg/day). Blood tests revealed a serum level of carbamazepine of 10.7mEq/l, which was over the therapeutic range (4.0-10.0mEq/l). Therefore, his carbamazepine dose was reduced, and with a reduction of the dose to 600mg/day, his disequilibrium and downbeat nystagmus gradually disappeared, along with a decrease in return of the serum level of carbamazepine to the therapeutic range. Therefore, we diagnosed the disequilibrium with downbeat nystagmus in this patient as having been caused by carbamazepine intoxication. Although carbamazepine is metabolized by CYP3A4 in the liver, elevated levels of the drug have been reported in cases of renal failure. As he also suffered from polycystic kidneys, we consider that the progressive renal dysfunction in our patient could have precipitated the carbamazepine intoxication.

Improving response rates and representativity in the CPI medical care index

Respondents’ low response rates that affect not only sample size but also sample composition have emerged as a central challenge in measuring consumer price change for medical care. In the case of medical care, insufficient responses from respondents have made getting an accurate mix of prices by payer type (self-pay, insurance, Medicare Part B) more difficult. This article summarizes recent methodological improvements to the medical care index that address a decline in response rates over the last two decades and an overrepresentation of self-pay price quotes.

Effects of Simulation-Based Practice Education on Learning Satisfaction, Immersion, and Self-Efficacy of Nursing Students

The purpose of this study is to understand the effects of simulation-based practice education on learning satisfaction, immersion, and self-efficacy. Using the method of one-group pretest-posttest experimental research, this study selected total 70 nursing students (3rd year) as research subjects. The final research subjects were total 63 students excluding seven people with insufficient responses. From March to April 2021, total eight sessions of simulation practice education (4 hours per session) were conducted once a week. In the effects of the program, the immersion, learning satisfaction, and self-efficacy were measured. Using the SPSS Window Version 25.0, the immersion, learning satisfaction, and self-efficacy were analyzed through the mean, standard deviation, and paired t-test. In the results of this study, the learning satisfaction (t=-2.06, p=.003), immersion (t=-10.61, p&lt;.001), and self-efficacy(t=-2.31, p= .024) were statistically significant. In the results of analyzing the correlations of immersion, learning satisfaction, and self-efficacy after the simulation practice education, the learning satisfaction showed significantly positive correlation with immersion (r= .647, p&lt;.001). The immersion also had positive correlation with self-efficacy(r= .438, p&lt;.001). The results of this study verified the improvement of immersion, learning satisfaction, and self-efficacy of nursing students after the simulation-based practice education. Thus, it would be necessary to develop the educational contents for various subjects, and also to expansively apply the simulation practice education.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Parental Perspectives on the Impact of the COVID-19 Pandemic on Infant, Child, and Adolescent Development.

The purpose of this study is to understand how families from diverse sociodemographic backgrounds perceived the impact of the pandemic on the development of their children. We used a multimethod approach guided by Bronfenbrenner's Ecological Systems Theory, which identifies 5 developmental systems (micro, meso, exo, macro, and chrono). Semistructured interviews were conducted in English or Spanish with parents living in 5 geographic regions of the United States between July and September 2021. Participants also completed the COVID-19 Exposure and Family Impact Survey. Forty-eight families participated, half of whose preferred language was Spanish, with a total of 99 children ages newborn to 19 years. Most qualitative themes pertained to developmental effects of the microsystem and macrosystem. Although many families described negative effects of the pandemic on development, others described positive or no perceived effects. Some families reported inadequate government support in response to the pandemic as causes of stress and potential negative influences on child development. As context for their infant's development, families reported a variety of economic hardships on the COVID-19 Exposure and Family Impact Survey, such as having to move out of their homes and experiencing decreased income. In addition to negative impacts, many parents perceived positive pandemic-attributed effects on their child's development, mainly from increased time for parent-child interaction. Families described economic hardships that were exacerbated by the pandemic and that potentially affect child development and insufficient government responses to these hardships. These findings hold important lessons for leaders who wish to design innovative solutions that address inequities in maternal, family, and child health.

Hyaluronic acid and multiwalled carbon nanotubes as bioink additives for cartilage tissue engineering

Articular cartilage and meniscus injuries are prevalent disorders with insufficient regeneration responses offered by available treatment methods. In this regard, 3D bioprinting has emerged as one of the most promising new technologies, offering novel treatment options. Additionally, the latest achievements from the fields of biomaterials and tissue engineering research identified constituents facilitating the creation of biocompatible scaffolds. In this study, we looked closer at hyaluronic acid and multi-walled carbon nanotubes as bioink additives. Firstly, we assessed the minimal concentrations that stimulate cell viability, and decrease reactive oxygen species and apoptosis levels in 2D cell cultures of normal human knee articular chondrocytes (NHAC) and human adipose-derived mesenchymal stem cells (hMSC-AT). In this regard, 0.25 mg/ml of hyaluronic acid and 0.0625 mg/ml of carbon nanotubes were selected as the most optimal concentrations. In addition, we investigated the protective influence of 2-phospho-L-ascorbic acid in samples with carbon nanotubes. Tests conducted on 3D bioprinted constructs revealed that only a combination of components positively impacted cell viability throughout the whole experiment. Gene expression analysis of COL1A1, COL6A1, HIF1A, COMP, RUNX2, and POU5F1 showed significant changes in the expression of all analyzed genes with a progressive overall loss of transcriptional activity in most of them.

Proteomics Investigation of Diverse Serological Patterns in COVID-19

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

Hydrochemical controls on arsenic contamination and its health risks in the Comarca Lagunera region (Mexico): Implications of the scientific evidence for public health policy.

Nearly half of the world's urban population depends on aquifers for drinking water. These are increasingly vulnerable to pollution and overexploitation. Besides anthropogenic sources, pollutants such as arsenic (As) are also geogenic and their concentrations have, in some cases, been increased by groundwater pumping. Almost 40 % of Mexico's population relies on groundwater for drinking water purposes; much the aquifers in semi-arid and arid central and northern Mexico is contaminated by As. These are agricultural regions where irrigation water is primarily provided from intenstive pumping of the aquifers leading to long-standing declines in the water table. The focus of this study is the main aquifer within the Comarca Lagunera region in Northern Mexico. Although the scientific evidence demonstrates that health effects are associated with long-term exposure to elevated As concentrations, this knowledge has not yielded effective groundwater development and public health policy. A multidisciplinary approach - including the evaluation of geochemistry, human health risk and development and public health policy - was used to provide a current account of these links. The dissolved As concentrations measured exceeded the corresponding World Health Organization guideline for drinking water in 90 % of the sampled wells; for the population drinking this water, the estimated probability of presenting non-carcinogenic health effects was >90 %, and the lifetime risk of developing cancer ranged from 0.5 to 61 cases in 10,000 children and 0.2 to 33 cases in 10,000 adults. The results suggest that insufficient policy responses are due to a complex and dysfunctional groundwater governance framework that compromises the economic, social and environmental sustainability of this region. These findings may valuable to other regions with similar settings that need to design and enact better informed, science-based policies that recognize the value of a more sustainable use of groundwater resources and a healthier population.

Annexin A1 Is Associated with Adverse Clinical Outcomes in Patients with COVID-19.

Severe coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation, vascular damage, and hypercoagulability. Insufficient responses of Annexin A1 (AnxA1), a pro-resolving inhibitor of neutrophil infiltration and activation, might contribute to a severe course of the disease. We longitudinally evaluated AnxA1's role in terms of inflammation, vascular damage, and clinical outcomes in a large prospective cohort of patients with COVID-19. AnxA1 was measured at presentation and during follow-up in the sera of 220 consecutive patients who presented at our hospital during the first wave. AnxA1 was significantly higher in the moderate and severe cases of COVID-19 compared to the healthy controls. Elevated AnxA1 was associated with markers of inflammation and endothelial damage. AnxA1 was significantly higher in patients with thrombotic events and ICU admission. Multivariable logistic regression indicated baseline AnxA1 (per ten units) as a predictor of thrombotic events. Linear mixed models predicted that AnxA1 tended to increase more steeply over time in patients without adverse events, with a statistically significant rise in patients without thrombotic events. These findings might reflect an insufficient increase in AnxA1 as a response to the excessive hyperinflammation in COVID-19. Future studies should evaluate whether hyperinflammation could be reduced through the administration of human recombinant AnxA1 or Ac2-26 peptide.

Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation Patients.

High-level BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) predicts failing immune control and BKPyV-associated hemorrhagic cystitis. To identify molecular markers of BKPyV replication and disease, we scrutinized BKPyV DNA-loads in longitudinal urine and plasma pairs from 20 HCT patients using quantitative nucleic acid testing (QNAT), DNase-I treatment prior to QNAT, next-generation sequencing (NGS), and tested cell-mediated immunity. We found that larger QNAT amplicons led to under-quantification and false-negatives results (P < .001). DNase-I reduced urine and plasma BKPyV-loads by >90% (P < .001), indicating non-encapsidated BKPyV genomes. DNase-resistant urine BKPyV-loads remained infectious in cell culture. BKPyV genome fragmentation of ≤250 bp impaired NGS coverage of genetic variation using 1000-bp and 5000-bp amplicons. Conversely, 250-bp amplicons captured viral minority variants. We identified genotype-specific and genotype-independent changes in capsid Vp1 or T-antigen predicted to escape from antibody neutralization or cytotoxic CD8 T-cells, respectively. Genotype-specific changes in immunodominant 9mers were associated with reduced or absent CD8 T-cell responses. Thus, failure to control BKPyV replication in HCT Patients may involve insufficient genotype-specific cytotoxic CD8 T-cell responses, potentially predictable by low neutralizing antibodies as well as genotype-independent immune escape. Our results provide new insights for patient evaluation and for designing immune protection through neutralizing antibodies, adoptive T-cell therapy, or vaccines.

Image-guided stent-directed irreversible electroporation for circumferential ablation in the rat esophagus.

Background: Irreversible electroporation (IRE) has been investigated in the alimentary tract; however, the lack of dedicated electrodes and insufficient tissue responses made its application limited. The aim of this study was to investigate the efficacy and safety of image-guided stent-directed IRE in the rat esophagus. Methods: The bipolar self-expandable electrode (SE) was developed using the braiding technique. A finite element analysis was performed to validate optimal electrical field strength for the rat esophagus. A total of 40 out of 50 rats received stent-directed IRE and were sacrificed at 10h, 3days, 7days, and 28days of 10 each. The remaining ten rats underwent a sham procedure. The outcomes of stent-directed IRE were assessed by esophagography and histological responses. Results: Stent-directed IRE was technically successful in all rats with mild muscle contraction. The heart rate dropped immediately and gradually recovered at 180s. TUNEL and caspase-3 with submucosal thickness significantly increased at 10h and Day 3 compared with those of the sham control (all p < 0.001). The thickness of epithelial layers with collagen deposition significantly decreased at 10h and Day 3 (all p < 0.001), however, increased at Day 7 compared with that of the sham control (all p < 0.05). The Ki67-positive deposition significantly increased at Day 3 and 7 compared with that of the sham control (all p < 0.001). All variables were similar to those of the sham control at Day 28. Conclusion: Image-guided stent-directed IRE was effective and safe in the rat esophagus. It seems to have effectively and evenly induced cell death and gradually recovered with cellular regeneration.

Polypharmacy Management of Antipsychotics in Patients with Schizophrenia

Schizophrenia is a chronic psychiatric disease that is characterized by psychotic symptoms, including positive, negative, affective, and aggressive symptoms, as well as cognitive dysfunction, and is primarily treated using drug therapy, the continuation of which is essential to prevent recurrence/recrudescence. Various second-generation antipsychotics with pharmacological properties or adverse events that differ from those of conventional antipsychotics have recently been introduced, and pharmaceutical management is required for drug efficacy assessments and adverse event monitoring/management of these drugs. Antipsychotic monotherapy (APM) is the gold standard treatment for schizophrenia and is recommended in various guidelines. However, a subgroup of patients with schizophrenia do not or only partially respond to APM. Therefore, antipsychotic polypharmacy (APP), in which ≥2 antipsychotics are combined, has been routinely utilized to compensate for insufficient responses to APM in clinical practice. APP has recently been proposed as an evidence-based treatment option, but does not consider clinicians' experience. However, the risk of APP-related adverse events is high. The application of APP needs to be carefully reviewed, whilst taking into consideration patient backgrounds. Furthermore, the risk of APP-related adverse events is higher in elderly patients than in the general population; therefore, caution is needed. This review discusses the merits of APP, matters that need to be considered, and a switch from APP to APM, and also focuses on the application of APP in clinical practice.